Pathophysiology of the Blood-Brain Barrier: Long Term Consequences of Barrier Dysfunction for the Brain (Fernstrom Foundation Series)

Neurology ◽  
1992 ◽  
Vol 42 (1) ◽  
pp. 267-267
Author(s):  
N. H. Greig
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
Long Term Consequences ◽  
The Brain

scholarly journals Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment

2019 ◽  
Vol 11 ◽  
pp. 117957351984065 ◽  
Author(s):  
Divine C Nwafor ◽  
Allison L Brichacek ◽  
Afroz S Mohammad ◽  
Jessica Griffith ◽  
Brandon P Lucke-Wold ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
The United States ◽  
Brain Barrier ◽  
Blood Brain ◽  
Systemic Inflammatory Disease ◽  
Sepsis Survivors ◽  
The Brain

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB’s role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

scholarly journals Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Francisco De Jesús Andino ◽  
Letitia Jones ◽  
Sanjay B. Maggirwar ◽  
Jacques Robert
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Frog Virus 3 ◽  
Frog Virus ◽  
Blood Brain ◽  
The Brain

scholarly journals The Dual Role of Microglia in Blood-Brain Barrier Dysfunction after Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1237-1249 ◽  
Author(s):  
Ruiqing Kang ◽  
Marcin Gamdzyk ◽  
Cameron Lenahan ◽  
Jiping Tang ◽  
Sheng Tan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Vital Role ◽  
Dual Role ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
M2 Microglia ◽  
The Brain

It is well-known that stroke is one of the leading causes of death and disability all over the world. After a stroke, the blood-brain barrier subsequently breaks down. The BBB consists of endothelial cells surrounded by astrocytes. Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. Microglia can also directly interact with endothelial cells and affect BBB permeability. In this review, we are going to discuss the mechanisms responsible for the dual role of microglia in BBB dysfunction after stroke.

Cadmium-induced alterations in blood- brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat

1996 ◽  
Vol 15 (5) ◽  
pp. 400-405 ◽  
Author(s):  
Arti Shukla ◽  
Girja S Shukla ◽  
RC Srimal
Keyword(s):  
Glutathione Peroxidase ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Albino Rats ◽  
Barrier Dysfunction ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

1 Male albino rats of 21 days age were exposed to 10 p.p.m. cadmium (CdCl2 salt) in drinking water, ad libitum, for 90 days. It increased the brain cadmium levels by 76% ( P < 0.05) and 165% ( P < 0.001) respec tively at 30 and 90 days of exposure compared to controls. 2 Cadmium increased blood - brain barrier permeability of fluoroscein dye (24%, P < 0.02) and the levels ofbrain microvessel malondialdehyde (31%, P<0.01) at 90 days of exposure. However, these parameters did not alter significantly at 30 days of exposure. 3 Increased activities of microvessel superoxide dismu tase (18%, P<0.02), glutathione peroxidase (20%, P<0.01) and catalase (28%, P<0.01) were observed at 30 days of exposure. 4 The continuation of the Cd treatment for 90 days decreased the levels of superoxide dismutase (30%, P<0.001), glutathione peroxidase (23%, P<0.005), catalase (25%, P < 0.005), glutathione reductase (18%, P < 0.02), vitamin E (20%, P < 0.01), glutathione (26%, P < 0.01), ascorbic acid (18%, P < 0.05) and ceruloplas min (13%, P<0.05) in the microvessal preparation compared to controls. 5 It appears that Cd-induced blood-brian barrier dysfunction may be related to the depletion of microvessel antioxidant substances along with in crease in lipid peroxidation at 90 days of exposure.

scholarly journals The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yiwei Wang ◽  
Huanhuan Sha ◽  
Leting Zhou ◽  
Yinan Chen ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Mast Cell ◽  
Blood Brain Barrier ◽  
Microglial Activation ◽  
Brain Barrier ◽  
Brain Disorders ◽  
Barrier Dysfunction ◽  
Cns Inflammation ◽  
Lps Challenge ◽  
Blood Brain ◽  
The Brain

Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, β-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and β-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.

scholarly journals EXPERIMENTAL INTESTINAL DYSBIOSIS IN RATS INCREASES THE PERMEABILITY OF THE BLOOD-BRAIN BARRIER AND INDUCES NEUROINFLAMMATION

2019 ◽  
Vol 19 (1S) ◽  
pp. 104-105
Author(s):  
V G Sergeyev ◽  
T N Sergeyeva
Keyword(s):  
Blood Brain Barrier ◽  
Intestinal Barrier ◽  
Alpha Synuclein ◽  
Brain Barrier ◽  
Local Inflammation ◽  
Barrier Dysfunction ◽  
Cellular Mechanisms ◽  
Blood Brain ◽  
Intestinal Dysbiosis ◽  
The Brain

The mammalian intestinal microbiota consists of bacteria, fungi and viruses, including bacteriophages. This complex ecosystem has dynamic stability. It is assumed that changes in the composition of the microbiota can cause intestinal barrier dysfunction and the development of a number of pathologies, including neurodegenerative diseases accompanied by neuroinflammation. The molecular and cellular mechanisms underlying such a relationship remain poorly understood. We hypothesized that bacteriophages cause intestinal dysbiosis, increased intestinal permeability and local inflammation. Bacterial factors (endotoxins, zonulin-like proteins) and local inflammation products (cytokines, alpha-synuclein protein) can enter the circulation and increase the permeability of the blood-brain barrier (BBB), which will cause neuro-inflammation and damage to neurons. In this study, we observed an increase in BBB permeability and induction of neuroinflammation in the brain after rectal administration of a bacteriophage cocktail (Microgen, Russia). The permeability of the BBB was judged by the volume of the vital dye (Evans blue) emerging from the bloodstream into the brain parenchyma, and the development of the neuroinflammatory response by increasing the number of immunohistochemically stained microglial and astroglial cells.

scholarly journals Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258199
Author(s):  
Leda Castaño Barrios ◽  
Ana Paula Da Silva Pinheiro ◽  
Daniel Gibaldi ◽  
Andrea Alice Silva ◽  
Patrícia Machado Rodrigues e Silva ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Behavioral Changes ◽  
Brain Barrier ◽  
Behavioral Alterations ◽  
Compulsive Disorder ◽  
Blood Brain ◽  
The Brain

The Apicomplexa protozoan Toxoplasma gondii is a mandatory intracellular parasite and the causative agent of toxoplasmosis. This illness is of medical importance due to its high prevalence worldwide and may cause neurological alterations in immunocompromised persons. In chronically infected immunocompetent individuals, this parasite forms tissue cysts mainly in the brain. In addition, T. gondii infection has been related to mental illnesses such as schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder, as well as mood, personality, and other behavioral changes. In the present study, we evaluated the kinetics of behavioral alterations in a model of chronic infection, assessing anxiety, depression and exploratory behavior, and their relationship with neuroinflammation and parasite cysts in brain tissue areas, blood-brain-barrier (BBB) integrity, and cytokine status in the brain and serum. Adult female C57BL/6 mice were infected by gavage with 5 cysts of the ME-49 type II T. gondii strain, and analyzed as independent groups at 30, 60 and 90 days postinfection (dpi). Anxiety, depressive-like behavior, and hyperactivity were detected in the early (30 dpi) and long-term (60 and 90 dpi) chronic T. gondii infection, in a direct association with the presence of parasite cysts and neuroinflammation, independently of the brain tissue areas, and linked to BBB disruption. These behavioral alterations paralleled the upregulation of expression of tumor necrosis factor (TNF) and CC-chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES) in the brain tissue. In addition, increased levels of interferon-gamma (IFNγ), TNF and CCL2/MCP-1 were detected in the peripheral blood, at 30 and 60 dpi. Our data suggest that the persistence of parasite cysts induces sustained neuroinflammation, and BBB disruption, thus allowing leakage of cytokines of circulating plasma into the brain tissue. Therefore, all these factors may contribute to behavioral changes (anxiety, depressive-like behavior, and hyperactivity) in chronic T. gondii infection.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

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